Skip Navigation



NDT Advance Access published online on January 14, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn758
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
24/7/2044    most recent
gfn758v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Goldberg, S.
Right arrow Articles by Miner, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldberg, S.
Right arrow Articles by Miner, J. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Glomerular filtration is normal in the absence of both agrin and perlecan–heparan sulfate from the glomerular basement membrane

Seth Goldberg1, Scott J. Harvey1, Jeanette Cunningham1, Karl Tryggvason2 and Jeffrey H. Miner1

1 Renal Division, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA 2 Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden

Correspondence and offprint requests to: Jeffrey H. Miner, Renal Division 8126, 660 S. Euclid Ave., St Louis, MO 63110, USA. Tel: +1-314-362-8235; Fax: +1-314-362-8237; E-mail: minerj{at}wustl.edu



  Abstract

Background. For several decades, it has been thought that the glomerular basement membrane (GBM) provides a charge-selective barrier for glomerular filtration. However, recent evidence has presented challenges to this concept: selective removal of heparan sulfate (HS) moieties that impart a negative charge to the GBM causes little if any increase in proteinuria. Removal of agrin, the major GBM HS-proteoglycan (HSPG), from the GBM causes a profound reduction in the glomerular anionic charge without changing the excretion of a negatively charged tracer. Perlecan is another HSPG present in the GBM, as well as in the mesangium and Bowman's capsule, that could potentially contribute to a charge barrier in the absence of agrin.

Methods. Here we studied the nature of the glomerular filtration barrier to albumin in mice lacking the HS chains of perlecan either alone or in combination with podocyte-specific loss of agrin.

Results. The results show significant reductions in anionic sites within the GBM in perlecan-HS and in perlecan-HS/agrin double mutants. Podocyte and overall glomerular architecture were normal, and renal function was normal up to 15 months of age with no measurable proteinuria. Moreover, excretion of a negatively charged Ficoll tracer was unchanged as compared to control mice.

Conclusions. These findings cast further doubt upon a critical role for the GBM in charge selectivity.

Keywords: charge selectivity; Ficoll; glomerular basement membrane; glomerular filtration; perlecan

Received for publication: 27.10.08
Accepted in revised form: 17.12.08


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.